1. Reuse of Single Use Devices CDRH/CBER MDUFMA Stakeholder Meeting Presented by: Barbara Zimmerman

2. Sec. 302 – Single-Use Medical Devices (SUDs) Certain reprocessed SUDs identified by FDA must include validation data. Validation data includes cleaning, sterilization, and functional performance data demonstrating substantial equivalence.

3. Requirements of Sec. 302 For reprocessed SUDs which are exempt from 510(k) requirements, determine which “critical” reprocessed SUDs are no longer exempt Federal Register notice- dated April 30, 2003 (List I) Federal Register notice- dated June 26, 2003 (added non-electric biopsy forceps to List I) Due date for validation data to be submitted to FDA – July 30 and Sept. 26, 2004

4. Requirements of Sec. 302 Determine which non-exempt reprocessed SUDs require validation data Federal Register notice- dated April 30, 2003 (List II) Due date for validation data to be submitted to FDA – January 30, 2004

5. Requirements of Sec. 302 For reprocessed SUDs which are exempt from 510(k) requirements, determine which “semi-critical” reprocessed SUDs are no longer exempt Federal Register notice- dated April 24, 2004 (List I) Due date for 510(k)s with validation data to be submitted to FDA – July 24, 2005

6. Comments Submitted to Docket Bundling of reprocessed SUDs Review Prioritization Scheme Update of Lists I and II to include additional devices Timeliness of FDAs review of validation data

7. SUPPLEMENTAL VALIDATION SUBMISSIONS for Reprocessed Single-Use Medical Devices (SUDs) Ginette Y. Michaud, MD Office of Device Evaluation November 18, 2004 Gaithersburg, Maryland

8. Supplemental Validation Submissions (SVSs) July 2003: guidance on the validation data to be submitted June of 2004, updated guidance with information on review timelines.

9. Supplemental Validation Submissions 53 SVSs anticipated accounting for 1800 device models 9 SVSs were not submitted – all NSE 44 SVSs received; 19 SE 12 SE for some models 11 NSE or withdrawn 2 under review

10. Supplemental Validation Submissions CDRH accounted for 1800 device models 52% found SE - may continue to be legally marketed 33% found NSE (no data or inadequate data submitted) 15% withdrawn by the reprocessor.

11. Supplemental Validation Submissions Reprocessed SUDs that were withdrawn or found NSE may no longer be legally marketed. Reprocessors of these SUDs may submit new 510(k) premarket notifications to FDA.

12. Supplemental Validation Submissions In completing MDUFMA mandate, CDRH: –accounted for 1800 SUD models –addressed complex scientific issues –resource intensive and interactive process –careful and thorough reviews –timely and scientifically grounded regulatory decisions

13. How can users access information on the status of their reprocessed SUDs? Users can determine which models are legally marketed and which ones are not. The status of previously cleared reprocessed SUDs appears on FDA’s Reuse website, at: (http://www.fda.gov/cdrh/reuse/) http://www.fda.gov/cdrh/reuse/

15. REPROCESSING OF SINGLE USE DEVICES (SUDS) MDUFMA Stakeholder’s Meeting November 18, 2004 Steven Turtil, M.S. FDA/CDRH/ODE/DAGID/INCB

16. 510(k) Data – Reprocessed SUDs With each application, data should be submitted and reviewed for: Cleaning Validation Cleaning Validation Sterilization Validation Sterilization Validation Functionality Testing Functionality Testing –No Standards –Standards Available –Guidance and Standards Available

17. How do we want to define “Clean” To allow for successful, subsequent sterilization steps. To limit to a minimum, the organic soil transfer from one patient to another. To prevent accumulation of residual soil (and to prevent the development of biofilms) after multiple cycles.

18. FDA Recommended Validation Data, Post-Simulated Use, for Cleaning of SUDs Body Contact Device Examples Blood PathOphthalmicTissueCompromised Skin EP Catheters Phacoemulsification Tips Biopsy Forceps, Arthroscopes, Fixation Devices Vascular Compression Devices (external) TEST TYPES Test soil to be selected and justified according to the intended use of the device Visual Inspection Total Protein Hemoglobin Carbohydrates Contrast Media (where appropriate) No Visible Soil

19. Table of Contents Cleaning Process: Instructions for technicians - highly variable between reprocessors. Cleaning Process Validation: What is it? –Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty? –Cleaning Validation Protocols: How are you going to test the Cleaning Process? –Test Protocols and Cleaning Endpoints And a summary of Sterility, Endotoxin and Detergent Residues

20. Cleaning Process Cleaning Instructions should specify: Point-of-Use Decontamination Disassembly, if possible Automated or Manual cleaning, or a combination – time, temperature, brushing duration, etc. Ultrasound – time, temperature, setting (high, medium, low) Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing) Intermediate Rinse Steps – time, temp., particular water quality specifications.

21. Table of Contents Cleaning Process: Instructions - highly variable between reprocessors. Cleaning Process Validation: What is it? –Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty? –Cleaning Validation Protocols: How are you going to test the Cleaning Process? –Test Protocols and Cleaning Endpoints And a summary of Sterility, Endotoxin and Detergent Residues

22. Table of Contents Cleaning Process: Instructions - highly variable between reprocessors. Cleaning Process Validation: What is it? –Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty? –Cleaning Validation Protocols: How are you going to test the Cleaning Process? –Test Protocols and Cleaning Endpoints And a summary of Sterility, Endotoxin and Detergent Residues

23. Table of Contents Cleaning Process: Instructions - highly variable between reprocessors. Cleaning Process Validation: What is it? –Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty? –Cleaning Validation Protocols: How are you going to test the Cleaning Process? –Test Protocols and Cleaning Endpoints And a summary of Sterility, Endotoxin and Detergent Residues

24. Table of Contents Cleaning Process: Instructions - highly variable between reprocessors. Cleaning Process Validation: What is it? –Artificial Soils and Simulated Use Protocols: How are you going to get the devices dirty? –Cleaning Validation Protocols: How are you going to test the Cleaning Process? –Test Protocols and Cleaning Endpoints And a summary of Sterility, Endotoxin and Detergent Residues

25. Cleaning Process Validation Use of actual clinical contamination as well as simulated organic soil that represents intended clinical exposure. Simulation of worst case clinical use conditions: –Inoculation sites should be most difficult to clean –Duration of exposure should mimic worst case –Articulations/Flextures/Manipulations, etc. Worst case cleaning conditions. Use of actual clinical contamination as well as simulated organic soil that represents intended clinical exposure. Simulation of worst case clinical use conditions: –Inoculation sites should be most difficult to clean –Duration of exposure should mimic worst case –Articulations/Flextures/Manipulations, etc. Worst case cleaning conditions. Cleaning Validation Protocols should support and confirm the effectiveness of the Routine Cleaning Instructions and should include consideration of:

26. Cleaning Validation Protocols Should Include WORST CASE consideration of: Automated, Manual or a combination – time, temperature, brushing duration Ultrasound – time, temperature, setting (high, medium, low) Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing). Intermediate Rinse Steps – time, temp., particular water quality specifications. Automated, Manual or a combination – time, temperature, brushing duration Ultrasound – time, temperature, setting (high, medium, low) Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing). Intermediate Rinse Steps – time, temp., particular water quality specifications.

27. Cleaning Validation Protocols Compare Cleaning Instructions with Validation Protocols If instructions say “Sonication 20 – 25 min.,” then validation should be for 20 min. or less. Examples (note set-points, tolerances): If instructions say “Not to exceed 12 devices per cleaning load,” then validation should be performed with 12 devices, or more.

28. Test Protocols and Cleaning Endpoints Specify the endpoints of cleaning, and data should meet them – at the end of its use-life. Visual Inspection should be part of both the routine cleaning and the cleaning validation (yet realize the limitations: e.g., lumens). Extraction method should be validated. Test methods should be validated. Specify the endpoints of cleaning, and data should meet them – at the end of its use-life. Visual Inspection should be part of both the routine cleaning and the cleaning validation (yet realize the limitations: e.g., lumens). Extraction method should be validated. Test methods should be validated.

29. Sterilization Standards are available for validation methods. –ISO 11134 – Industrial Moist Heat –ISO 11135 – Ethylene Oxide Applicants should provide a “summary of the sterilization process design and validation activities.” Use of routine methods for evaluation of endotoxins on medical devices, for those devices required to be labeled as such. Testing should be conducted on final, sterilized product (as always). Standards are available for validation methods. –ISO 11134 – Industrial Moist Heat –ISO 11135 – Ethylene Oxide Applicants should provide a “summary of the sterilization process design and validation activities.” Use of routine methods for evaluation of endotoxins on medical devices, for those devices required to be labeled as such. Testing should be conducted on final, sterilized product (as always).

30. Bundling Reprocessing a group of closely related device models based on validation data for a “representative” worst case model. How was the worst case device selected? –Were all materials considered? –All geometric variances? –Is there validation data to support this? –Or a scientifically valid justification? An especially tricky issue: slight differences in materials may result in different surface characteristics, and unexpected consequences with regard to cleaning effectiveness. Bundling between different manufacturers’ products should be validated or scientifically justified, because device designs can be very dissimilar. Reprocessing a group of closely related device models based on validation data for a “representative” worst case model. How was the worst case device selected? –Were all materials considered? –All geometric variances? –Is there validation data to support this? –Or a scientifically valid justification? An especially tricky issue: slight differences in materials may result in different surface characteristics, and unexpected consequences with regard to cleaning effectiveness. Bundling between different manufacturers’ products should be validated or scientifically justified, because device designs can be very dissimilar.

32. MDUFMA STAKEHOLDERS MEETING Reuse of Single Use Devices Panel – Compliance Update November 18, 2004

33. Reprocessor Inspection Update - Hospitals Over 225 inspections conducted since 8/2000 Three types of Inspections: –Routine surveillance, i.e. f/u to hospital registration –“For Cause” i.e. f/u to informant reports – Sample of hospitals based on their responses to a contractor survey Findings: –Most hospitals were either not reprocessing or promised to discontinue –A few early inspections led to FDA correspondence; one Warning Letter and two untitled letters

34. Reprocessor Inspection Update – Third Party Firms  In the 1990s, there were 15-20 reprocessing firms Earlier inspections commonly found GMP problems in validation, purchasing controls & component controls 17 Warning Letters have issued 2 injunctions were filed; both firms went out of business All currently registered firms (5) have been inspected; all recent inspections found in substantial compliance

35. Compliance Follow-up to NSEs and Withdrawals Calls made to all applicants (5 firms) to determine withdrawal plans for distributed product All applicants have withdrawn/are withdrawing product Inspection assignment developed to verify discontinuance of reprocessing Inspection to cover special concerns raised by Office of Device Evaluation, i.e. packaging Inspection assignments request review of validation for the firm’s key processes